Anle138b Clinical Phase 1 Studies: Food Effect, Safety and Tolerability as well as Pharmacokinetics in Parkinson´s Disease Patients

Study Rationale: 
Clumps of the protein alpha-synuclein, called Lewy bodies, are a hallmark of Parkinson’s disease and a promising target for therapeutic development. Anle138b is a drug-like compound that inhibits alpha-synuclein clumping (called aggregation) and holds promise to slow the progression of Parkinson’s. Initial data from healthy volunteers after intake of anle138b as a capsule in the fasted state showed good blood levels and safety. Before testing anle138b in long-term studies in patients focusing on clinical efficacy, the investigators want to learn if anle138b can be taken with food and if there is any difference in safety or blood level profiles in patients with Parkinson’s compared to healthy volunteers.

Hypothesis:
Our hypothesis is that there is no difference in terms of safety, tolerability or blood levels of anle138b between people with Parkinson’s and healthy volunteers, which could influence trial design or dosing, and that anle138b can be taken with food.

Study Design:
To assess the safety, tolerability and blood levels of anle138b administered as a capsule in patients with mild to moderate Parkinson’s, the team plans to treat three cohorts of patients with different dose levels in an ascending order for seven days. The study (including dosing) will be double-blinded and placebo-controlled. Starting dose and dose increase, respectively, will be determined based on available data. To study the effect of food, on day 9, study participants will take anle138b with a standard breakfast and the investigators will compare potential changes in their drug levels to the healthy volunteers who took the drug first in a fasting condition and after excretion with a standardized breakfast on a separate day.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
This study will provide the basis for determining the best possible dosing regimen for a clinical study to test the efficacy of anle138b in people with Parkinson’s. It will also provide a reference needed for in-trial dose adaptations if needed. Hence, this trial will be crucial to provide the best chance of success with future trials testing if anle138b can slow or stop the progression of Parkinson’s.

Next Steps for Development:
Based on the data from this trial, the team will finalize ongoing plans for disease modification studies in multiple system atrophy (MSA) and Parkinson’s.